4 research outputs found
Estimation of genetic diversity in viral populations from next generation sequencing data with extremely deep coverage
In this paper we propose a method and discuss its computational
implementation as an integrated tool for the analysis of viral genetic
diversity on data generated by high-throughput sequencing. Most methods for
viral diversity estimation proposed so far are intended to take benefit of the
longer reads produced by some NGS platforms in order to estimate a population
of haplotypes. Our goal here is to take advantage of distinct virtues of a
certain kind of NGS platform - the platform SOLiD (Life Technologies) is an
example - that has not received much attention due to the short length of its
reads, which renders haplotype estimation very difficult. However, this kind of
platform has a very low error rate and extremely deep coverage per site and our
method is designed to take advantage of these characteristics. We propose to
measure the populational genetic diversity through a family of multinomial
probability distributions indexed by the sites of the virus genome, each one
representing the populational distribution of the diversity per site. The
implementation of the method focuses on two main optimization strategies: a
read mapping/alignment procedure that aims at the recovery of the maximum
possible number of short-reads; the estimation of the multinomial parameters
through a Bayesian approach, which, unlike simple frequency counting, allows
one to take into account the prior information of the control population within
the inference of a posterior experimental condition and provides a natural way
to separate signal from noise, since it automatically furnishes Bayesian
confidence intervals. The methods described in this paper have been implemented
as an integrated tool called Tanden (Tool for Analysis of Diversity in Viral
Populations).Comment: 30 pages, 5 figures, 2 tables, Tanden is written in C# (Microsoft),
runs on the Windows operating system, and can be downloaded from:
http://tanden.url.p
Analysis of the Origin and Evolutionary History of HIV-1 CRF28_BF and CRF29_BF Reveals a Decreasing Prevalence in the AIDS Epidemic of Brazil
HIV-1 subtype B and subtype F are prevalent in the AIDS epidemic of Brazil. Recombinations between these subtypes have generated at least four BF circulating recombinant forms (CRFs). CRF28_BF and CRF29_BF are among the first two BF recombinants being identified in Brazil and they contributed significantly to the epidemic. However, the evolution and demographic histories of the CRFs are unclear.A collection of gag and pol sequences sampled within Brazil was screened for CRF28_BF-like and CRF29_BF-like recombination patterns. A Bayesian coalescent framework was employed to delineate the phylogenetic, divergence time and population dynamics of the virus having CRF28_BF-like and CRF29_BF-like genotype. These recombinants were phylogenetically related to each other and formed a well-supported monophyletic clade dated to 1988-1989. The effective number of infections by these recombinants grew exponentially over a five-year period after their emergence, but then decreased toward the present following a logistic model of population growth. The demographic pattern of both recombinants closely resembles those previously reported for CRF31_BC.We revealed that HIV-1 recombinants of the CRF28_BF/CRF29_BF clade are still circulating in the Brazilian population. These recombinants did not exhibit a strong founder effect and showed a decreasing prevalence in the AIDS epidemic of Brazil. Our data suggested that multiple URFs may also play a role in shaping the epidemic of recombinant BF HIV-1 in the region